Is CASR p.Asn802Ser (c.2405A>G) pathogenic?

CASR p.Asn802Ser (c.2405A>G) is classified Pathogenic/Likely pathogenic in CASR (ClinVar, Multiple submitters, 8 submitters; last evaluated 2026-09-02). AlphaMissense: likely benign (0.1435); Very rare (popmax 0.004%, afr); Associated with CASR-related disorder.

What condition is associated with CASR p.Asn802Ser (c.2405A>G)?

CASR p.Asn802Ser (c.2405A>G) is associated with CASR-related disorder, familial hypocalciuric hypercalcemia 1, neonatal severe primary hyperparathyroidism (ClinVar).

How common is CASR p.Asn802Ser (c.2405A>G) in the general population?

CASR p.Asn802Ser (c.2405A>G) is very rare (popmax 0.004%, afr) (gnomAD).

What do computational predictors say about CASR p.Asn802Ser (c.2405A>G)?

AlphaMissense predicts likely benign (score 0.1435) — an in-silico prediction, not a clinical call.

CASR p.Asn802Ser

c.2405A>G · rs140022350 · VCV379931

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 8 submitters

AlphaMissense

likely benign

0.1435 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.004%, afr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

CASR-related disorder

Computational evidence

Protein change
AlphaMissense	0.1435	likely benign ⚠ discordant with ClinVar
REVEL	0.669	pathogenic-leaning
SaProt	LLR -9.35	tolerated
⇒ REVEL calls this damaging; AlphaMissense and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 2.1, phastCons 1
Regional constraint	o/e 0.66	unconstrained · MANE · 660 bp · p 1.4e-08 · regional, not allelic
Overall
CADD	27.8	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.004% African / African-American · 3/74,934 alleles

Filtering AF 0.00106% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000495%

Overall 0.000805% 13/1,614,010 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.004%	24,978
South Asian	0.0011%	91,088
European (non-Finnish)	0.000763%	131,116

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: CASR
Protein: p.Asn802Ser
Coding: c.2405A>G
MANE Select: NM_000388
dbSNP: rs140022350
Type: single nucleotide variant
Location: chr3:122284359 (GRCh38)
Gene constraint: LOEUF 0.469 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 76.01 · 31 PDB
Residue 802: a UniProt-annotated variant site (in hhc1; impaired homodimerization; impaired cell membrane localization); a UniProt-annotated variant site (in hypoc1; increased g protein-coupled receptor signaling pathway); a UniProt-annotated variant site (in hhc1; decreased g protein-coupled receptor signaling pathway); the 'intracellular loop 3 (icl3)' region; a turn

Full CASR gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

CASR-related disorder

Also linked: familial hypocalciuric hypercalcemia 1 neonatal severe primary hyperparathyroidism autosomal dominant hypocalcemia 1 epilepsy, idiopathic generalized, susceptibility to, 8 familial hypocalciuric hypercalcemia

Similar variants

CASR p.Asn802Asp Uncertain significance ★★ ⚠ same residue
CASR p.Asn802= Likely benign ★★ same residue
CASR p.Asn802His Likely pathogenic ★ ⚠ same residue
CASR p.Asn802Ile Pathogenic ★ same residue
CASR c.1378-1G>C Likely pathogenic ★★ same condition
CASR c.1608+1G>A Likely pathogenic ★★ same condition
CASR c.1609-2A>G Likely pathogenic ★★ same condition
CASR c.186-1G>T Pathogenic ★★ same condition

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/casr-p-asn802ser (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown